Department of Neurology.
Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit.
Neuroreport. 2021 Mar 24;32(5):359-366. doi: 10.1097/WNR.0000000000001598.
Cerebrolysin has been shown to promote neurovascular protection and repair in preclinical models of stroke and neural injury and is demonstrating promise for stroke and neural injury therapeutic application in the clinic. The effect of Cerebrolysin on the human cerebral endothelial cell function has not been investigated. Using an in-vitro cerebral endothelial cell permeability assay and western blot analyses of tight junction and proinflammatory and procoagulant proteins, the present study showed that tissue plasminogen activator (tPA) and fibrin substantially impaired human cerebral endothelial cell barrier function and increased permeability, which persisted for at least 24 h. western blot analysis revealed that tPA and fibrin significantly increased proinflammatory and procoagulation proteins of intercellular adhesion molecule 1, high mobility group box 1, tumor necrosis factor α and phosphorylated nuclear factor kappa B-p65, and significantly reduced tight junction proteins zonular 1, occludin and claudin. However, Cerebrolysin significantly diminished and reversed tPA- and fibrin-impaired endothelial cell permeability, which was associated with significant reductions of tPA- and fibrin-augmented proinflammatory and procoagulation proteins and significant elevations of tPA- and fibrin-decreased tight junction proteins. The beneficial effect of Cerebrolysin appears specific because cerebroprotein hydrolysate, with a distinct peptide composition, failed to show the reduction of tPA- and fibrin-impaired permeability. These data indicate that cererbrolysin has a therapeutic effect on tPA- and fibrin-impaired cerebral endothelial cell permeability by reducing proinflammatory and procoagulation proteins and by elevating tight junction proteins.
Cerebrolysin 已被证明可促进中风和神经损伤的临床前模型中的神经血管保护和修复，并且在中风和神经损伤的治疗应用中显示出前景。Cerebrolysin 对人脑血管内皮细胞功能的影响尚未得到研究。本研究通过体外脑血管内皮细胞通透性测定和紧密连接以及促炎和促凝蛋白的 Western blot 分析表明，组织纤溶酶原激活物（tPA）和纤维蛋白显著损害了人脑血管内皮细胞的屏障功能并增加了通透性，至少持续 24 小时。Western blot 分析显示，tPA 和纤维蛋白显著增加了细胞间黏附分子 1、高迁移率族蛋白 1、肿瘤坏死因子α和磷酸化核因子 kappa B-p65 的促炎和促凝血蛋白，并显著降低了紧密连接蛋白 zonular 1、occludin 和 claudin。然而，Cerebrolysin 显著减少并逆转了 tPA 和纤维蛋白引起的内皮细胞通透性受损，这与 tPA 和纤维蛋白增强的促炎和促凝血蛋白的显著减少以及 tPA 和纤维蛋白降低的紧密连接蛋白的显著升高有关。Cerebrolysin 的有益作用似乎是特异性的，因为具有不同肽组成的脑蛋白水解物未能显示出减少 tPA 和纤维蛋白引起的通透性受损。这些数据表明，Cerebrolysin 通过降低促炎和促凝血蛋白并升高紧密连接蛋白，对 tPA 和纤维蛋白引起的脑血管内皮细胞通透性具有治疗作用。
